Drugs and radiation therapy are conventional approaches to treating cancer. One example is Cisplatin or cis-diamminedichloroplatinum(II) (CDDP), which is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer and ovarian cancer), lymphomas and germ cell tumors. It was the first member of its class, which now also includes carboplatin and oxaliplatin. Cisplatin acts by crosslinking DNA in various different ways, in a manner that is not cell cycle specific, making it impossible for rapidly dividing cells to duplicate their DNA for mitosis. The damaged DNA sets off DNA repair mechanisms, which activate apoptosis when repair proves impossible.
Another example is Paclitaxel, more commonly referred to by the trade name Taxol®, which is a member of the larger family of compounds known as taxanes. Currently, paclitaxel is used in the treatment of breast, ovarian, certain non-small-cell lung cancers, and Kaposi's sarcoma. This potent anti-neoplastic drug; binds to the N-terminal region of β-tubulin and promotes the formation of highly stable microtubules that resist depolymerization, thus preventing normal cell division and arresting the cell cycle at the G2/M phase. The microtubule damage induces apoptosis through a JNK-dependent pathway in the early phase followed by a JNK-independent pathway, perhaps related to the activation of protein kinase A or of Raf-1 kinase, that results in phosphorylation of Bcl-2. Major metabolite in human liver microsome is 6α-hydroxypaclitaxel (6α-OHP). This enzymatic conversion can be used as a potential marker reaction for human CYP2C8.
An additional cancer treatment modality that has been introduced recently is Photo-Dynamic Therapy (PDT). PDT is a rapidly growing area of medical treatment. The diseases that can be successfully treated by PDT include skin cancer, brain tumors, tumors under the surface of the skin, and tumors located on the lining of internal organs. Photodynamic Therapy involves the use of light-activated dyes (photosensitizers) that preferably localize in target cells (e.g. in tumors) but not in normal, healthy cells. Photosensitizers utilize energy from treatment light to produce a cytotoxic oxygen species which kills cancerous or diseased cells. This toxic oxygen species is not a radical but is actually an excited state of oxygen. The excited state is more reactive than ordinary oxygen, and the atoms are in a different quantum spin state than is normally the case. PDT may also work by destroying the blood vessels that feed the cancer cells and by helping the immune system to attack the cancer.
PDT, using the drug Photofrin®, has now been approved as a therapy for a limited number of applications in various parts of the world including the UK and it is now clear that there are some indications where PDT is at least as good as and possibly better than alternative treatments. However it has to be emphasized that PDT is still largely an experimental therapy and is currently only applicable to a very small range of patients. This limitation results in part from the fact that most tumors are located in areas where light from external sources is not effective. To overcome this problem catheters, having light sources at their tip, are inserted through the skin (or a natural cavity like the GI tract) into the body.
Depending on the part of the body being treated, the photosensitizing substances are either injected intravenously into the diseased area or applied to the skin. The photosensitizer selectively accumulates in the tumor region. After allowing time for the accumulation to occur, a light source is applied to the area to be treated. The light causes the drug to react with oxygen, which forms a chemical that kills the cancer cells. Because blood and melanin are relatively absorptive in the shorter visible wavelengths, it is preferable to use infrared light. Therefore, the ideal photosensitizer has an absorbance peak in the infrared part of the spectrum. This ensures that light used in the treatment is able to penetrate maximally through healthy tissue to arrive at the tumor. However, other wavelengths can be selected according to the absorption and sensitivity of the various substances used.
Light-emitting diodes (LEDs) are considered an appropriate light source for PDT. LEDs have a relatively narrow bandwidth (usually 20 to 30 nm), and are available in a wide range of wavelengths, including the near infrared (NIR) and infrared (IR)—from 650 nm to 950 nm. The flexibility provided by chip-on-board techniques makes it possible to fabricate customized LED illuminators for various PDT applications.
In more established Photodynamic Therapy treatments, such as skin cancer therapy, the diseased zone is exposed to an LED area light for a precisely calculated exposure time. In newer or more experimental areas of treatment, miniature LED arrays are actually implanted into tissue, or are placed on catheters and are moved through the body. In some procedures, LED dice are fixed to a flexible, compact substrate. However, for any tumor situated more than about 1 cm away from the accessible surface, the light source must be implanted. Since LEDs must be hooked up to a power supply in order to function, this generally requires that lead wires connect the LED or other light source to an external device. As the duration of an effective treatment may be long, even weeks, the wires that penetrate the skin may lead to contamination, dysfunction and significant discomfort.